We have performed this study to investigate the modulatory effect of thymoquinone (TQ), the Nigella sativa active compound, on erythrocyte lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine- (DMH-) induced colon carcinogenesis after initiation in male Wistar rats. Rats exposed to DMH showed an increase of malondialdehyde and conjugated diene levels, and an augmentation of enzyme activities like catalase, glutathione peroxidase, and superoxide dismutase activities was also noted. The TQ pretreatment restored the parameters cited above to near-normal values. However, the posttreatment shows an activity similar as that presented by DMH. Therefore, our investigation revealed that TQ was a useful compound preventing DMH-induced erythrocyte damages.